Trauma remains the leading cause of death between the ages of 1 and 44. Head injury and multiple organ failure with sepsis are key factors in the high morbidity and mortality. Organ failure include respiratory distress, impaired host defense, hepatic insufficiency, altered vascular permeability, metabolic disturbances and cardiopulmonary dysfunction accompanying head injury. Our goal is to understand the pathophysiology of multiple organ failure in trauma and burn patients and to use this understanding to develop new modes of therapy. This goal will be accomplished by the unique interaction of a multi-disciplinary and multi-institutional team of basic and clinical scientists. Our goals are to: 1) test the hypothesis that pulmonary microaggregation can alter vascular permeability and cause V/Q maldistribution in septic and injured patients without head injury; 2) quantify the synthesis rate of fibronectin after injury or in septic-injured patients using stable isotope infusion techniques in order to test the hypothesis that prolonged fibronectin deficiency may be related to impaired synthesis; 3) test the hypothesis that brain injury and hypoxemia cause maldistribution of cerebral blood flow; 4) test the hypothesis that altered transvascular fluid flux accompanys gas exchange abnormalities in patients after head injury; 5) test in the clinical setting the therapeutic value of a closed-loop controlled ventilator, whose operation will be based on the continuous monitoring of PO2, PCO2, and non-invasive measurements of cardiac output; and 6) test the hypothesis that robuts and Bayesian mathematical methods can be employed to statistically assess small samples of data efficiency. Achievement of these goals will advance our understanding of the pathophysiology of trauma and burn and contribute to the development of effective modalities of therapy.